Method for preparing biological valve material by means of double-bond polymerization after aldehyde crosslinking, as well as biological valve material and use

Abstract

Disclosed is a method for preparing biological valve material by means of double-bond polymerization after aldehyde crosslinking, as well as the biological valve material and use therefor. The preparation method includes: step S 110, contacting the biomaterial with an aldehyde-based crosslinking agent solution for crosslinking; Step S 120: soaking the biomaterial processed in Step S 110 in a solution containing a first functional monomer for reaction to introduce first carbon-carbon double bonds; wherein the first functional monomer has first carbon-carbon double bonds and an epoxyethane group; and Step S 200 , performing polymerization of the carbon-carbon double bonds under an action of an initiator to obtain the biological valve material. In this disclosure, double bonds are introduced into the glutaraldehyde crosslinked biological valve material, and polymerization of the double bonds is further initiated, improving the stability of the glutaraldehyde crosslinked material and further reducing the risk of calcification caused by structural degradation.

What is claimed is: 
     
         1 . A method for preparing a biological valve material by means of double-bond polymerization after aldehyde crosslinking, comprising:
 Step S 110 : contacting biomaterial with an aldehyde-based crosslinking agent solution for crosslinking;   Step S 120 : soaking the biomaterial treated in step S 110  in a solution containing a first functional monomer for a chemical reaction to introduce first carbon-carbon double bonds;   wherein the first functional monomer has the first carbon-carbon double bonds and an ethylene oxide group; and   Step S 200 : performing polymerization of the carbon-carbon double bonds under an action of an initiator to obtain the biological valve material.   
     
     
         2 . The method according to  claim 1 , wherein the aldehyde-based crosslinking agent is glutaraldehyde or formaldehyde. 
     
     
         3 . The method according to  claim 1 , wherein the biomaterial is an animal tissue selected from one or more of the following: pericardium, valve, intestinal valve, meninges, lung valve, blood vessel, skin or ligament. 
     
     
         4 . The method according to  claim 3 , wherein the animal tissue is a fresh animal tissue or a decellularized biological tissue. 
     
     
         5 . The method according to  claim 1 , wherein the step S 200  comprises:
 adding the initiator to a system treated in a previous step; or 
 taking the biomaterial treated in the previous step out and directly or after washing soaking the biomaterial treated in the previous step in a solution containing the initiator. 
 
     
     
         6 . The method according to  claim 1 , wherein the initiator is a single initiator or a mixed initiator. 
     
     
         7 . The method according to  claim 6 , wherein the mixed initiator is:
 a mixture of ammonium persulfate and sodium bisulfite, or a mixture of ammonium persulfate and sodium sulfite, or a mixture of sodium persulfate and sodium sulfite, or a mixture of potassium persulfate and sodium sulfite, or a mixture of sodium persulfate and sodium bisulfite, or a mixture of potassium persulfate and sodium bisulfite, or a mixture of potassium persulfate and tetramethylethylenediamine, or a mixture of ammonium persulfate and tetramethylethylenediamine, or a mixture of sodium persulfate and tetramethylethylenediamine; and a concentration of each component in the mixture is in a range of 1 to 100 mM.   
     
     
         8 . The method according to  claim 7 , wherein the single initiator is any component of the mixed initiator. 
     
     
         9 . The method according to  claim 1 , wherein in step S 200 , a double-bond polymerization time is in a range of 3 to 24 h. 
     
     
         10 . The method according to  claim 1 , wherein the first functional monomer is at least one selected from a group consisting of allyl glycidyl ether, glycidyl methacrylate and glycidyl acrylate. 
     
     
         11 . The method according to  claim 1 , wherein in step S 110 :
 a w/w concentration of the aldehyde-based crosslinking agent solution is in a range of 0.1% to 5%; and a crosslinking time is in a range of 0.5 h to 120 h.   
     
     
         12 . The method according to  claim 1 , wherein in step S 120 :
 a w/w concentration of the first functional monomer in the solution containing the first functional monomer is in a range of 1% to 10%; and a reaction time is in a range of 2 to 120 h.   
     
     
         13 . The method according to  claim 1 , wherein the solution containing the first functional monomer only contains the first functional monomer and a solvent that does not participate in chemical reaction. 
     
     
         14 . The method according to  claim 1 , wherein the solvent in the solution containing the first functional monomer is one or more of the following: water, physiological saline, a neutral pH buffer, and an aqueous solution of any one of methanol, ethanol, ethylene glycol, propanol, 1,2-propanediol, 1,3-propanediol, isopropanol, butanol, isobutanol, 1,2-butanediol, 1,3-butanediol, 1,4-butanediol, and glycerol. 
     
     
         15 . A biological valve material prepared by the method according to  claim 1 . 
     
     
         16 . A biological valve material prepared by the method according to  claim 5 . 
     
     
         17 . A biological valve material prepared by the method according to  claim 10 . 
     
     
         18 . A biological valve, comprising a stent and leaflets, wherein the leaflets are made of the biological valve material according to  claim 15 . 
     
     
         19 . The biological valve according to  claim 18 , wherein the biological valve is a prosthetic heart valve. 
     
     
         20 . An interventional system, comprising a prosthetic heart valve and a catheter assembly. wherein the prosthetic heart valve is delivered by the catheter assembly after being folded. wherein the prosthetic heart valve comprises a stent and leaflets, and the leaflets are made of the biological valve material according to  claim 15 .